Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China.

Objective: This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection. Methods: Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results: A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day ( P < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference ( P > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed ( P > 0.05). Conclusion: The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14-28 d) on the immunization potential.

45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis.

There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948-2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.

Australian consensus statement on doxycycline post-exposure prophylaxis (doxy-PEP) for the prevention of syphilis, chlamydia and gonorrhoea among gay, bisexual and other men who have sex with men.

INTRODUCTION: Doxycycline post-exposure prophylaxis (doxy-PEP) involves consuming 200 mg of doxycycline up to 72 hours after a condomless sex act to reduce the risk of bacterial sexually transmitted infections (STIs). Recent clinical trials of doxy-PEP have demonstrated significant reductions in syphilis, chlamydia and, to a lesser degree, gonorrhoea among gay, bisexual and other men who have sex with men (GBMSM). There is a high level of interest in doxy-PEP in the GBMSM community and, in response, the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) held a national consensus conference with the aim of creating preliminary guidance for clinicians, community, researchers and policy makers. MAIN RECOMMENDATIONS: There was broad agreement that doxy-PEP should be considered primarily for the prevention of syphilis in GBMSM who are at risk of this STI, with a secondary benefit of reductions in other bacterial STIs. At the end of the consensus process, there remained some disagreement, as some stakeholders felt strongly that doxy-PEP should be considered only for the prevention of syphilis in GBMSM, and that the risk of increasing antimicrobial resistance outweighed any potential benefit from reductions in other bacterial STIs in the target population. The national roundtable made several other recommendations for clinicians, community, researchers and policy makers, as detailed in this article. ASHM will support the development of detailed clinical guidelines and education materials on doxy-PEP (www.ashm.org.au/doxy-pep). CHANGES IN MANAGEMENT AS A RESULT OF THIS CONSENSUS STATEMENT: For GBMSM at high risk of syphilis, and perhaps other bacterial STIs, clinicians may consider prescribing doxy-PEP for a limited period of time, followed by a review of ongoing need. Unlike human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP), doxy-PEP may not be suitable as a population-level intervention and should instead be used more selectively.

Mitoquinone mesylate as post-exposure prophylaxis against SARS-CoV-2 infection in humans: an exploratory single center pragmatic open label non-randomized pilot clinical trial with matched controls.

BACKGROUND: An ongoing important need exists to rapidly develop novel therapeutics for COVID-19 that will retain antiviral efficacy in the setting of rapidly evolving SARS-CoV-2 variants and potential future development of resistance of SARS-COV-2 to remdesivir and protease inhibitors. To date, there is no FDA-approved treatment for post-exposure prophylaxis against SAR-CoV-2. We have shown that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has antiviral activity against SARS-CoV-2 in vitro and in SARS-CoV-2 infected K18-hACE2 mice. METHODS: In this exploratory, pragmatic open label clinical trial (ClinicalTrials.gov identifier NCT05381454), we studied whether Mito-MES is an effective post-exposure prophylaxis treatment in people who had high-grade unmasked exposures to SARS-CoV-2 within 5 days prior to study entry. Participants were enrolled in real-world setting in Los Angeles, United States between May 1 and December 1, 2022 and were assigned to either mito-MES 20 mg daily for 14 days (n = 40) or no mito-MES (controls) (n = 40). The primary endpoint was development of SARS-CoV-2 infection based on 4 COVID-19 diagnostic tests [rapid antigen tests (RATs) or PCR] performed during the study period (14 days post exposure). FINDINGS: Out of 40 (23 females; 57.5%) study participants who took Mito-MES, 12 (30%) developed SARS-CoV-2 infection compared to 30 of the 40 controls (75%) (difference -45.0%, 95% confidence intervals (CI): -64.5%, -25.5%). Out of 40 (19 females; 47.5%) study participants in the control group, 30 (75.0%) had at least one positive COVID-19 diagnostic test and 23 (57.5%) were symptomatic. With regards to key secondary outcomes, among symptomatic SARS-CoV-2 infections, the median duration of viral symptoms was lower in the Mito-MES group (median 3.0, 95% CI 2.75, 3.25) compared to the control group (median 5.0, 95% CI 4.0, 7.0). None of the study participants was hospitalized or required oxygen therapy. Mito-MES was well tolerated and no serious side effect was reported in any study participant. INTERPRETATION: This work describes antiviral activity of mito-MES in humans. Mito-MES was well tolerated in our study population and attenuated transmission of SARS-CoV-2 infection. Given established safety of Mito-MES in humans, our results suggest that randomized control clinical trials of Mito-MES as post-exposure prophylaxis against SARS-CoV-2 infection are warranted. FUNDING: This work was supported in part by National Institutes of Health grant R01AG059501 (TK), National Institutes of Health grant R01AG059502 04S1 (TK), NIH/National Center for Advancing Translational Sciences (NCATS) UCLA CTSI Grant Number UL1TR001881 and California HIV/AIDS Research Program grant OS17-LA-002 (TK).

Rabies post-exposure prophylaxis in the emergency department.

STUDY OBJECTIVES: Rabies is a zoonotic single-stranded RNA lyssavirus that can cause acute infections of the central nervous system (CNS) including encephalomyelitis, encephalitis, and meningoencephalitis that is progressively fatal. Rabies is more common in developing countries, but approximately 23,000 people in the United States (US) are estimated to have been exposed or to have received post exposure prophylaxis (PEP) yearly. Nebraska Medicine follows the Advisory Committee on Immunization Practices (ACIP) guidelines for the vaccination series, as well as the 20 units/kg administration of immunoglobulin (RIG). Nebraska Medicine Medical Center (NMC) and Bellevue Medical Center (BMC) treat the scheduling of the complete rabies vaccine series differently. At both campuses, patients receive their immunoglobulin and first vaccine in the Emergency Department (ED). At NMC, patients are scheduled to receive the remainder of their vaccination series at the outpatient infusion center by the ED pharmacist. At BMC, the subsequent vaccinations are given as "Nurse Only" return visits to the ED. The objective of this study was to compare patient compliance of two different processes for follow-up rabies vaccine series completion. This project's primary aim was to determine the rate of patient compliance for follow up rabies vaccine doses. The secondary aims of this project were to determine if there was a difference in patient follow-up compliance between the two campuses, patient specific factors that impact compliance, and potential cost savings if a dose rounding protocol for RIG was utilized. METHODS: This retrospective chart review was completed as a quality improvement project. Data from patients who had received either rabies immunoglobulin and/or a rabies vaccine, were >18 years of age, and were not admitted were collected for a 3-year period from July 1, 2019, to June 30, 2022. Data were abstracted from the patient's EMR (electronic medical records) using a SQL (Structured query language) query of pre-identified data elements. When unable to abstract with SQL query, data elements were manually abstracted. All data abstracted was collated and descriptive analysis performed. RESULTS: A total of 723 individual encounters were identified during the study period. After combining rabies series for each individual patient, 173 unique patients remained. After exclusions were applied, 143 patients were included: 104 patients from NMC, and 39 from BMC. For the primary outcome, appropriate completion between the two campuses was 78.3%. When comparing the two campuses, completion rates were higher at NMC (82% vs. 69%), although not statistically significant (p = 0.12). Appropriate completion of vaccine series was statistically significant for both payor and exposure type. Application of a dose rounding policy with those >45 kg, rounding to the nearest vial, as well as rounding down if at the midpoint interval, 56 fewer vials would have been used between the two campuses. This would have resulted in a potential cost savings of $57,928.64 over the study period.

Doxycycline post-exposure prophylaxis could theoretically select for resistance to various antimicrobials in 19 pathobionts: an in silico analysis.

OBJECTIVES: Doxycycline post exposure prophylaxis (PEP) has been shown to reduce the incidence of bacterial STIs. However, if there is genetic linkage between resistance to tetracycline and other antimicrobials, then it could also select for resistance to these other antimicrobials. We therefore undertook to evaluate if there is an association between the minimum inhibitory concentrations (MICs) of tetracycline and other antimicrobials in 19 clinically important bacterial species. METHODS: Mixed-effects linear regression was used to assess if minocycline MICs were associated with the MICs of eight other antimicrobials (ceftriaxone, ampicillin, oxacillin, vancomycin, erythromycin, levofloxacin, amikacin, and trimethoprim-sulfamethoxazole) in 19 bacterial species in the Antimicrobial Testing Leadership and Surveillance (ATLAS) database. RESULTS: With the notable exception of vancomycin, where no association was found, strong positive associations were typically found between the MICs of minocycline and each of the eight antimicrobials in each of the species assessed. For example, the minocycline MICs of all the Gram-positive species were positively associated with ampicillin, ceftriaxone, oxacillin and erythromycin MICs (all P-values < 0.001). The only exceptions were ampicillin for Streptococcus pyogenes and ceftriaxone for S. dysgalactiae, where no significant associations were found. Similarly in the Gram-negative species, the minocycline MICs of all the species except Haemophilus influenzae and Stenotrophomonas maltophilia were positively associated with the MICs of ceftriaxone, ampicillin, levofloxacin and amikacin (all P-values < 0.001). CONCLUSIONS: There is a theoretical risk that doxycycline PEP could select for resistance not only to tetracyclines but to a range of other antimicrobials in each of the 19 pathobionts assessed.

Real-world evidence of rabies post-exposure prophylaxis in Serbia: Nation-wide observational study (2017-2019).

BACKGROUND: Rabies remains a deadly zoonotic disease, primarily prevalent in Eastern European countries, with a significant global burden in Asia and Africa. Post-exposure prophylaxis (PEP) is critical to prevent clinical rabies. Serbia, a country with a relatively low animal rabies incidence, has been implementing a 4-dose Essen PEP regimen for 13 years. This real-world study aimed to assess the effectiveness of the 4-dose Essen regimen, considering demographic and clinical factors, after WHO Category III exposure. METHOD: The study included 601 patients who received the 4-dose Essen PEP and 79 who received an additional 5th dose. RESULTS: Age emerged as a critical factor influencing seroconversion rates after the 4-dose regimen, with older individuals exhibiting lower RVNA titers. Logistic regression indicated a 3.18% decrease in seroconversion odds for each added year of age. The Cox proportional hazards mixed model highlighted age-related risks, with age groups 45-60 and 75-92 at the highest risk of non-seroconversion. Human Rabies Immune Globulin (HRIG) administration was associated with lower RVNA values after the 4-dose regimen, suggesting interference with vaccine immunogenicity among people who received larger doses of HRIG. CONCLUSIONS: This study provides valuable real-world evidence for rabies PEP in a non-homogeneous population with potential comorbidities. The results underscore the importance of optimizing PEP strategies, particularly in older individuals, and reconsidering HRIG dosing to improve seroconversion rates.

Knowledge of Pre- and Postexposure Prophylaxis for HIV Prevention Among Internal Medicine Residents in the United States.

Prescription rates of pre-exposure prophylaxis (PrEP) have remained low among noninfectious disease providers in the United States despite almost a decade since their introduction. For future primary care doctors, residency is the optimal time to build practice patterns around HIV prevention. We assessed baseline knowledge of PrEP in specific pre- and post-exposure prophylaxis content areas among internal medicine trainees who completed the Physician Education and Assessment Center HIV learning module between 2013 to 2020 (N = 12,060). Resident baseline PrEP knowledge was universally low; despite rising awareness of antiretroviral therapy for PrEP in successive years following the nadir of 41% in 2014, still only 56% of residents affirmed this means of HIV prevention by 2020. Knowledge remained limited regardless of academic year, local HIV prevalence, or training program type. Online module completion increased competence across all content areas. There is still a deficit in HIV prevention knowledge across U.S. internal medicine residents, suggesting insufficient education and exposure to HIV-related care.

Feasibility of post-exposure-prophylaxis with single-dose rifampicin and identification of high prevalent clusters in villages' hyperendemic for leprosy in Senegal.

INTRODUCTION: Senegal is a leprosy low-endemic country with nine villages known to be hyperendemic with a leprosy incidence rate above 1,000 per million inhabitants. We aim to implement a door-to-door screening strategy associated with the administration of a single-dose-rifampicin (SDR) as post-exposure prophylaxis (PEP) to household and social contacts in these villages and to identify spatial clustering and assess the risk of leprosy in population according to the physical distance to the nearest index-case. METHODS: From October/2020 to February/2022 active door-to-door screening for leprosy was conducted in nine villages. Using an open-source application, we recorded screening results, demographic and geographic coordinate's data. Using Poisson model we analysed clustering and estimated risk of contracting leprosy in contacts according to the distance to the nearest new leprosy patient. RESULTS: In nine villages, among 9086 contacts listed, we examined 7115. Among 6554 eligible contacts, 97.8% took SDR. We found 39(0.64%) new leprosy cases among 6,124 examined in six villages. Among new cases, 21(53.8%) were children, 10(25.6%) were multibacillary and 05(12.8%) had grade 2 disability. The prevalent risk ratio and 95% confidence intervale(95%CI) adjusted by village were 4.2(95%CI 1.7-10.1), 0.97(95%CI 0.2-4.4), 0.87(95%CI 0.2-25), 0.89(95%CI 0.3-2.6) and 0.70(95%CI 0.2-2.5) for the contacts living in the same household of an index case, 1-25m, 26-50m, 51-75m and 76-100m compared to those living at more than 100m respectively. We identified nine high prevalent clusters including 27/39(69%) of new cases in 490/7,850(6%) inhabitants, with relative risks of 46.6(p-value = 0.01), and 7.3, 42.8, 8.2, 12.5, 11.4, 23.5, 22.3, and 14.6 (non-significant p-values). CONCLUSIONS: Our strategy has proved the feasibility of active screening for leprosy in contacts and the introduction of PEP for leprosy under programmatic conditions. Only individuals living in the same household as the leprosy patient had a significant risk of contracting leprosy. We documented nine clusters of leprosy that could benefit from tailored control activities while optimizing resources.

Exposure History, Post-Exposure Prophylaxis Use, and Clinical Characteristics of Human Rabies Cases: A Twelve-Year Retrospective Review at a Tertiary Facility in Ghana.

BACKGROUND: Robust monitoring and reporting systems for rabies are lacking thus increasing the risk of underreporting. Highlighting the rabies cases brings to bear the needed urgent attention for more efforts at preventing and controlling the disease. OBJECTIVE: To describe the epidemiological characteristics of patients managed for clinical rabies at the largest referral facility in Ghana. METHODS: A retrospective single-center hospital-based chart review and data extraction were conducted for persons managed for clinical rabies infection at the Korle-Bu Teaching Hospital from January 2008 to December 2019. Data analysis was done using STATA. Descriptive statistics were used to summarize the epidemiological and clinical characteristics. Fisher's exact test, the Kruskal-Wallis test, and Spearman's correlation coefficient were used to explore significant associations. RESULTS: A total of 28 cases were recorded over the period of review. All of them died and most (68%) of them were males. Twenty-one percent of them were less than 15 years old. Their median age interquartile range (IQR) was 31 years (25.5 years) and the median incubation period for rabies (IQR) was 60 days (60 days). The source of rabies for cases was mainly dog bites. The vaccination status of all the animals could not be ascertained. Majority (80%) of the patients took neither anti-rabies vaccine nor immunoglobulin as post-exposure prophylaxis after the dog bite. The median time of admission before death (interquartile range) was 2 days (2 days). Majority (82%) of the cases were furious rabies. CONCLUSION: Attention should be directed at mass vaccination of dogs as dog bites are common. Ensuring availability and access to post-exposure prophylaxis (PEP) is also critical in averting rabies-related deaths.

CONTEXTE: Des systèmes de surveillance et de déclaration robustes pour la rage font défaut, augmentant ainsi le risque de sousdéclaration. Mettre en lumière les cas de rage suscite l'attention urgente nécessaire pour redoubler d'efforts dans la prévention et le contrôle de la maladie. OBJECTIF: Décrire les caractéristiques épidémiologiques des patients traités pour une rage clinique dans le plus grand établissement de référence au Ghana. MÉTHODES: Une revue rétrospective des dossiers médicaux et une extraction de données basées à l'hôpital ont été réalisées pour les personnes traitées pour une infection à la rage clinique à l'Hôpital d'Enseignement Korle-Bu de janvier 2008 à décembre 2019. L'analyse des données a été effectuée à l'aide de STATA. Des statistiques descriptives ont été utilisées pour résumer les caractéristiques épidémiologiques et cliniques. Le test exact de Fisher, le test de Kruskal-Wallis et le coefficient de corrélation de Spearman ont été utilisés pour explorer les associations significatives. RÉSULTATS: Un total de 28 cas ont été enregistrés sur la période examinée. Tous sont décédés et la plupart d'entre eux (68%) étaient des hommes. Vingt et un pour cent d'entre eux avaient moins de 15 ans. Leur âge médian (plage interquartile) était de 31 ans (25,5 ans) et la période d'incubation médiane de la rage (plage interquartile) était de 60 jours (60 jours). La principale source de rage pour les cas était principalement les morsures de chiens. Le statut vaccinal de tous les animaux n'a pas pu être déterminé. La majorité (80%) des patients n'ont pris ni vaccin antirabique ni immunoglobuline en prophylaxie post-exposition après la morsure de chien. Le délai médian d'admission avant le décès (plage interquartile) était de 2 jours (2 jours). La majorité (82%) des cas étaient atteints de rage furieuse. CONCLUSION: L'attention devrait être dirigée vers la vaccination de masse des chiens car les morsures de chien sont courantes. Assurer la disponibilité et l'accès à la prophylaxie post-exposition (PPE) est également crucial pour éviter les décès liés à la rage. MOTS-CLÉS: Rage, morsure de chien, post-exposition, prophylaxie, vaccination de masse.

The PEP++ study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission.

BACKGROUND: Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. METHODS: The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 - 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 - 600 mg) and clarithromycin (150 - 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox' proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. DISCUSSION: Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. TRIAL REGISTRATION: NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060.

Longitudinal predictors of post-exposure prophylaxis awareness among latino sexual minority men in South Florida.

Biomedical tools for HIV prevention such as post-exposure prophylaxis (PEP) continue to be underutilized by subgroups experiencing significant HIV inequities. Specifically, factors associated with both PEP awareness and uptake both cross-sectionally and longitudinally are under-researched, despite PEP being a part of the United States' Plan for Ending the HIV Epidemic. The current study examined longitudinal predictors of PEP awareness among Latino sexual minority men (LSMM) living in South Florida. This current study (N = 290) employed hierarchal linear modeling across three timepoints (baseline, 4-months, 8-months) to assess within-person and between-person effects over time for several psychosocial and structural factors. Most participants (67.5%) reported little to no awareness of PEP at baseline with general PEP awareness growing slightly across the study (60.5% reporting little to no awareness of PEP at 8 months). Results of the final conditional model suggest significant within-person effects of PrEP knowledge (p = 0.02) and PrEP self-efficacy (p < 0.001), as well as a significant positive between-person effect of PrEP knowledge (p < 0.01) on PEP awareness. Between-person HIV knowledge was also a significant predictor in this model (p = 0.01). This longitudinal analysis of LSMM's PEP awareness indicates that more must be done to increase PEP awareness among this subgroup. Future studies should explore how to build on existing interventions focused on HIV and PrEP knowledge and PrEP self-efficacy to incorporate information about PEP to increase the reach of this effective biomedical HIV prevention tool.

JYNNEOS™ effectiveness as post-exposure prophylaxis against mpox: Challenges using real-world outbreak data.

BACKGROUND: JYNNEOSTM vaccine has been used as post-exposure prophylaxis (PEP) during a mpox outbreak in New York City (NYC). Data on effectiveness are limited. METHODS: Effectiveness of a single dose of JYNNEOSTM vaccine administered subcutaneously ≤ 14 days as PEP for preventing mpox disease was assessed among individuals exposed to case-patients from May 22, 2022-August 24, 2022. Individuals were evaluated for mpox through 21 days post-exposure. An observational study was conducted emulating a sequence of nested "target" randomized trials starting each day after exposure. Results were adjusted for exposure risk and race/ethnicity. Analyses were conducted separately based on last (PEPL) and first (PEPF) exposure date. We evaluated the potential to overestimate PEP effectiveness when using conventional analytic methods due to exposed individuals developing illness before they can obtain PEP (immortal time bias) compared to the target trial. RESULTS: Median time from last exposure to symptom onset (incubation period) among cases that did not receive PEPL was 7 days (range 1-16). Time to PEPL receipt was 7 days (range 0-14). Among 549 individuals, adjusted PEPL and PEPF effectiveness was 19 % (95 % Confidence Interval [CI], -54 % to 57 %) and -7% (95 % CI, -144 % to 53 %) using the target trial emulation, respectively, and 78 % (95 % CI, 50 % to 91 %) and 73 % (95 % CI, 31 % to 91 %) using conventional analysis. CONCLUSIONS: Determining PEP effectiveness using real-world data during an outbreak is challenging. Time to PEP in NYC coupled with the observed incubation period resulted in overestimated PEP effectiveness using a conventional method. The target trial emulation, while yielding wide confidence intervals due to small sample size, avoided immortal time bias. While results from these evaluations cannot be used as reliable estimates of PEP effectiveness, we present important methodologic considerations for future evaluations.

Analysis of HIV drug prophylaxis services cascade in healthcare workers: a cross-sectional study in China.

BACKGROUND: Human immunodeficiency virus (HIV) drug prophylaxis, including post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP), has not yet been generally recognized and accepted by the whole society in China, and the utilization coverage among high-risk populations is low. Healthcare workers (HCWs) are important to the promotion and implementation of HIV drug prophylaxis strategy. This study analyzed the HIV drug prophylaxis services cascade (knowledge, attitude, and service) in HCWs, and explored the correlations between PEP and PrEP. METHODS: A cross-sectional study was conducted among 1066 HCWs in 20 designated hospitals for HIV antiretroviral therapy in 20 cities in China. We collected information on participants' essential characteristics, HIV drug prophylaxis services cascade (knowledge, attitude, and service) and so on. The Chi-square test was used to analyse whether the differences and correlations between categorical variables were statistically significant, and Pearson contingency coefficient was used to analyse the strength of correlations. Multivariable logistic regression was used to analyse associated factors. RESULTS: Among three stages of HIV drug prophylaxis services cascade, a high percentage of 1066 participants had knowledge of HIV drug prophylaxis (PEP: 78.2%, PrEP: 80.0%). Of them, almost all had supportive attitudes towards HIV drug prophylaxis (PEP: 99.6%, PrEP: 98.6%). Only about half of them would provide HIV drug prophylaxis services (PEP: 53.5%, PrEP: 48.5%). There were positive correlations between knowledge of PEP and PrEP (r = 0.292), between attitudes toward PEP and PrEP (r = 0.325), and between provision of PEP services and PrEP services (r = 0.555) in HCWs. CONCLUSIONS: There was a positive correlation between PEP and PrEP in HCWs. At the stage of providing HIV drug prophylaxis services, training, advocacy and education for HCWs, should be targeted and also combine PEP and PrEP to maximize the effects, so as to improve the enthusiasm of HCWs to provide HIV drug prophylaxis services.

Development of a Pharmacy Point-of-Dispensing Toolkit for Anthrax Post-Exposure Prophylaxis for Allegheny County Postal Workers.

CONTEXT: The Centers for Disease Control and Prevention (CDC) and the US Postal Service (USPS) consider anthrax to be a potential threat to USPS workers. A county health department-owned pharmacy supports local USPS response in the event of an exposure. The pharmacy team identified the need to review and update the local anthrax response plan. PROGRAM/POLICY: A Pharmacy Point-of-Dispensing Toolkit and response plan for initial 10-day post-exposure antibiotic prophylaxis was developed for use by a local health department in the event of a mass anthrax exposure at a US Post Office sorting facility. The pharmacist's role in medical countermeasures planning for anthrax exposure is also discussed to illustrate how pharmacists' medication expertise can be utilized. EVALUATION: The CDC's Public Health Preparedness Capabilities: National Standards for State and Local Planning framework and inputs from an interprofessional stakeholder team were used to develop a Medical Countermeasures Response Plan and Implementation Toolkit for mass point-of-dispensing (POD) in the event of an anthrax exposure. IMPLEMENTATION AND DISSEMINATION: Stakeholders attended a USPS Community Partner Training event where additional revisions to the toolkit were made. The toolkit and standing order are now implemented at the local health department to be reviewed and updated on a yearly basis by health department leadership. DISCUSSION: Pharmacists can use their medication expertise and experience with patient education to design emergency response plans focused on increasing patient safety and medication adherence. Pharmacists should be involved in emergency response and medical countermeasures planning that involve medications.

[Presentations for HIV post-exposure prophylaxis in emergency departments: guideline and recommendations]. / HIV-Postexpositionsprophylaxe in der Notaufnahme: Vorgehen, Tipps & Tricks.

Patients often present to emergency departments after potential or confirmed exposure to human immunodeficiency virus (HIV) asking for recommendations concerning the initiation of post-exposure prophylaxis (PEP). These presentations may occur after occupational as well as non-occupational exposure. PEP entails taking a triple antiretroviral therapy for 28-30 days. If taken early (ideally within 2 h, but no later than 72 h) and as indicated, HIV infection can be prevented with a high level of probability. Since these presentations occur around the clock, they require basic expertise on the part of the emergency department staff regarding its indication and its side effects as well as standardized procedures in the emergency department to not delay initiation. Patients should present to an infectious disease outpatient clinic or practice specialized in HIV in order to have the indication reviewed by a specialist and, if necessary, adapted to complex cases with the aim of making individual case decisions. This review article aims to summarize core statements of the 2022 German-Austrian guideline on HIV post-exposure prophylaxis and to give emergency department staff necessary knowledge to safely and correctly begin PEP.

Human T-lymphotropic virus type 1 and antiretroviral therapy: practical considerations for pre-exposure and post-exposure prophylaxis, transmission prevention, and mitigation of severe disease.

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with substantial risk of secondary (often life-threatening) disease for the estimated 10 million to 20 million people infected globally. Despite a clear need, no HTLV-1-specific vaccine or antiretroviral therapy has been developed to date. Instead, existing public and primary health-care interventions inadequately focus on infection prevention and management of secondary diseases. In this Personal View, we discuss the evidence that exists to support the sensitivity of HTLV-1 to antiretroviral therapies approved by the US Food and Drug Administration for the treatment of HIV-1, how this sensitivity is affected by clinically relevant virological and immunological features, and additional practical considerations for the use of antiretroviral therapies in the context of HTLV-1.